Metabolism reaction of dairy cows to xylazine injection during manipulated plasma metabolites

Xylazine is widely used in human and animal for different purposes such as anesthetics and analgesics in surgery. This component induces sedative, muscle relaxation and analgesic in veterinary. Xylazine is a α-2 agonist which causes cardiovascular and respiratory problem in animals. There is evidence that xylazine injection changed metabolites and endocrine in different species. In early lactation, the onset of copious milk production would bring about hepatic metabolic overloud to meet the energy and nutrient requirements for milk production. Elevation of energy and nutrient requirements for maintenance and milk synthesis cannot fulfill the feed intake, which consequently causes a negative energy balance (NEB) in early lactation in dairy cows. During a NEB, low plasma glucose concentrations are observed, while concomitantly concentrations of plasma free fatty acids (FFA) and subsequently ketone bodies are increased. Our earlier studies confirmed that manipulated insulin, glucose, and BHB concentrations, through infusion, changed plasma metabolites and endocrine in mid-lactating dairy cows, affected systemic/ local mammary metabolism, and immune response of the mammary gland. Based on our previous results and proved effects of xylazine injection on metabolism, this study aimed to assess the effects of xylazine injection on dairy cow metabolism alongside the change in some of blood metabolites and endocrine.
Material and The study was carried out on 24 clinically healthy multiparous (3.5 ± 0.10) Holstein dairy cows at 28 ± 0.3 (MEAN ± SD) wks in milk. Cows were free of mastitis throughout the experimental period. Animals were housed in tie stalls two weeks before the start of experiment as adaptation period. Animals were fed ad libitum with good quality hay, an addition protein- and energy-rich concentrate fed to them according to their energy and protein requirements twice daily. They received minerals (50 g/ cow) per day. Fresh water was available entire the experimental period. The cows were milked twice a day at 0530 h and 1600 h. Treatment infusion includs: an insulin infusion to induce hypoglycemia (2.5 ± 0.1 mmol/L; HypoG, n=5), an insulin combined glucose infusion to study effects of sole insulin at concurrently normal glucose concentration (EuG, n=6), a Na-DL-β-OH-butyrate to obtain plasma BHBA concentration between 1.5 to 2.0 mmol/L (HyperB, n=5) comparable to those in spontaneous hyper ketonemia (above 1.2 mmol/L), and a 0.9 % NaCl infusion (NaCl, 20 mL/h) as control group (n=8). On day before the start of infusion two indwelling intravenous catheters (Cavafix® Certo® Splittocan®, B. Braun Melsung AG, Germany) with a length of 32 cm and a diameter of 16 G were fixed in both jugular veins. The clamped infusions (56 h) started at 0900 am day one and continued to 0500 pm two days later. AS reported earlier (Kreipe et al. 2011; Vernay et al. 2012; Zarrin et al. 2013, 2014a,b) this study divided to two parts include: 48 h metabolites infusion to investigate the effects of manipulated metabolites concentration on metabolism and immune responses to metabolites infusion, and an addition 8 h to challenge mammary gland with lipopolysaccharide of E.coli (LPS) to investigate immune response simultaneously whit metabolite changing in dairy cows. At 47 h of infusion (1 h) before the intra-mammary LPS challenge to obtain mammary biopsies, a single dose of xylazine (16 μg/kg of BW) was injected. Blood samples were taken before (0 time) and 1 h after the xylazine injection. Plasma metabolites concentrations were measured enzymatically by commercial kits. Plasma insulin was measured by radioimmunoassay (RIA), and plasma glucagon concentrations were measured by using a commercial RIA kit. Changes of metabolites were evaluated by GLM procedure of SAS. Differences in plasma metabolites and endocrine parameters between before and after xylazine injection and between treatments were evaluated using the MIXED procedure of SAS with time points (0 and 1 h) and treatments (EuG, HyperB, HypoG, and Control) as fixed effects. Value presented as Mean ± SEM.
As expected, plasma glucose concentrations decreased before xylazine injection (2.25 ± 0.1 mmol/L; P The xylazine effects are different during the change of metabolites. Unchanged glucose concentration in HypoG and EuG is due to inhibitory effect of insulin on glucose elevation. Considering increasing glucose concentration in two animal groups without change in insulin and glucagon concentration, it can be speculated that other mechanisms than endocrine regulation contributes to glucose homeostasis.